Module C Flashcards
What layer of embryo does nervous system develop from?
Ectoderm
What triggers neural induction?
interaction with the mesoderm
What does the neural tube form from?
Neural plate
Function of BMP in early neurogenesis
Suppresses neural differentiation and promotes the
formation of epidermal tissue
What is the Function of Chordin and Noggin?
- Block the action of BMP
- allow for a selection of ectodermal cells to form the neural PLATE
Where do the signalling proteins Chordin and Noggin come frm?
Henson’s node
At what time in embryogenesis does the neural plate form?
by 2 ½ weeks of development
Describe the development of neural tube.
1) Infolding of neural plate by changes in the shapes of
the cells of the neural ectoderm , pinching at apices and expanding their bases ( not increase in cell number)
2) beginning in the middle and moving both rostrally and caudally
A failure of the tube to close rostrally leads to ________
anencephaly (lack neocortex)
Failure of the tube to close caudally leads to _________
spina bifida (part of the meninges or spinal cord protrudes through the spinal column)
Where does the neural crest cells develop from?
pinches off from the margins of the neural groove as it closes to become the neural tube
What does the neural tube and neural crest cells form
Neurons and glial cells
What type of proteins do Homeobox genes encode?
Transcription factors
What part of the brain develop segmentally
Rhombencephalon aka hindbrain
What causes the segmentation in development of hindbrain
Several genes whose pattern of expression at early stages in development correlates with the segmental boundaries of the hindbrain
Where is the Homeobox located?
conserved stretch of DNA in Homeotic genes
What do Homeobox encode
encodes a sequence of 60 amino acids that recognize and bind to specific DNA sequences in a series of subordinate genes
Master control genes aka
Hox genes
Function of Hox genes in Vertebrate embryo
creating structures appropriate to a particular anterior-posterior position
_____ and _____ Hox genes in humans
emx and otx
Genetic abnormalities of emx develop _______
schizencephaly, (deep crevices in cortex)
Genetic defects in otx develop _______
epilepsy
what determines the pattern of Hox gene expression?
longitudinal gradient of retinoic acid
Where is Retinoic acid produced?
Henson’s node
Henson’s node equivalent in avian and mammalian embryos
Spemann organizer
How does retinoic acid effect Hox genes?
- activate transcription of Hox genes
- there are systematic differences in the sensitivity of different Hox genes to retinoic acid
How is the retinoic acid gradient established?
diffusion of retinoic acid from Hensen’s node establishes a gradient along the short length of the embryo
What is the floor plate?
a band of specialized cells, lies along the ventral midline of the spinal cord
Signals from the ______, induce ventral spinal cord characteristics
Notochord (lies ventral to neural tube)
Describe pattern established by notochord
- ventral midline of the spinal cord===> Floorplate
- Adjacent regions of the neural tube give rise to ===> motoneurons,
- more dorsal regions===> interneurons
- the most dorsal region===> neural crest
___________ protein produced by notochord to induce ventral development of neural tube
Sonic hedgehog
________ secreted by ectodermal cells dorsal to the developing spinal cord and it induces the specification of
cells that lie in the dorsal horn
BMP (yea really!!!)
Other groups of neurons induced by Sonic Hedge hog
- serotoninergic neurons in the anterior hindbrain,
- dopaminergic neurons in the posterior midbrain,
- oculomotor neurons in the anterior midbrain
Cells of the neural tube are oriented _______
Radially
Steps of cell proliferation.
1) Cell nucleus migrates to the tube’s inner or ventricular surface
2) The pial end of the cell detaches
3) The cell divides
4) The nuclei of the daughters migrate toward the outer surface as the cells reattach to that surface
How do neurons migrate?
along Radial Glia
Older cells are found closer to _________ surface
external or pial surface
Radial glia are brief lived during development but are still found in 2 locations in adults
1) adult retina as Muller cells
2) cerebellum as Bergman glia
What does Neuronal birthdating done with?
timed pulses of tritiated thymidine
Neuronal birthdating shows that the larger cells are _______
older
All neurons in the brain are born before birth with 2 exceptions:
1) Granule cells in the cerebellum
2) Olfactory neurons
Which proteins mediating neuronal migration along radial glia?
1) neural glycoprotein astrotactin
2) specific isoforms of the extracellular matrix adhesion molecule receptor integrin
How do GnRH neurons migrate into CNS?
Along axonal tracts;
moving from the olfactory pit, an ectodermal derivative (placode) that gives rise to the nasal
epithelium, into the hypothalamus
What causes Kallmann’s syndrome?
migration fails to occur during development as a result of malformation of the olfactory placode
Symptoms of Kallmann’s syndrome?
no sense of smell and fail to mature sexually
Neural crest cells use neither Radial glia nor axonal tracts. How do they migrate?
along pathways marked by laminin
After migration, maturation of neuron depends on _________
its environment
What is Leukemia Inhibiting Factor (LIF)?
A peptide released by the muscle cells causes the change in phenotype of the crest cells and induces differentiation of cells in the immune system
What peptide induces differentiation of immune system?
LIF
Describe Axonal growth
1) The tip of the growing axon is enlarged to form the growth cone
2) It moves across and through the substrate, extending the fiber by adding membrane.
3) dynamic, interactive process in which projections from the growth cone (filopodia) extend and move to contact other cells and the substrate.
4) Receptors on the axon surface interact with specific molecules of the substrate.
5) In some cases growth cones may release enzymes to help clear a path and change the substrate.
6) Diffusible molecules released by cells along the pathway may also attract the growing axon
Axons that cross in the anterior commissure in the spinal cord are attracted there by a diffusible substance known as
Netrin
Netrin is released by
Floor plate
Molecule found in surrounding material that promotes neurite growth
Laminin
Where is Laminin found?
1) along pathways that axons follow as they extend
their processes in the developing nervous system
2) synthesized by Schwann cells after injury
Protein needed for layers of Schwann cell membranes to wrap and seal themselves around developing axons
PMP-22 (peripheral myelin protein)
In what hereditary disease is PMP-22 is not normal, peripheral myelin fails to form properly?
Charcot-Marie-Tooth disease
What is genetic defect in Charcot Marie Tooth Disease?
substitution of a glycine by aspartate
Formation of axon bundles is called
Fasciculation
What is responsible for fasicualtion
- Neural Cell Adhesion Molecules (N-CAMs) in the developing axons’ membranes
- binds to itself and thus causes axons to stick to one another
What is function of Agrin released by nerve cells that innervate the skeletal muscle ?
Receptors aggregate at the endplate, extrasynaptic sensitivity decreases
What happens to sensitivity after denervation?
-The sensitivity spreads again, but the focal sensitivity at the endplate and the acetylcholinesterase molecules located there are not lost
Role of Nerve Growth Factor in neuronal development
1) Enhance the outgrowth of neurites from sensory and sympathetic neurons (dorsal root ganglia)
2) essential for their survival as well.
Role of NGF in adult neurons
Regualtes synthesis of Norepi by inducing two enzymes required for its synthesis: tyrosine hydroxylase and
dopamine b-hydroxylase
How is NGF taken up by neurons?
retrograde transport from nerve terminals to the cell soma
Protein that is homologous to NGF that promotes the survival of dorsal root ganglion neurons and maintains CNS connections of sensory neurons
brain-derived neurotrophic factor (BDNF)
BNDF and NGF belong to what family of growth fatcors
neurotrophins
Basic structure of neurotrophins
dimers of a small basic peptide, held together by disulfide linkages between the conserved cysteine residues
Other neurotrophins
NT-3,NT-4/5, and NT-6
What neurotrophins are needed by neural crest cells and sensory neurons in dorsal root and trigeminal ganglia for proliferation, differentiation, and survival BEFORE they innervate targets?
BDNF or NT-3
What is the source of neurotrophins early in development?
neurons themselves and by the mesenchymal tissues through which the sensory axons grow
After sensory neurons reach their targets what is the source of NGF
Target cell produces NGF and neurons begin to express NGF receptors
What are the 2 types of neurotrophin receptors found on the surface of their target neurons?
1) low affinity (Kd = 10-9M) fast NGF receptor or p75
2) There are also high affinity (Kd = 10-11M) receptors
Where are the low affinity neurotrophin receptors found?
Both neurons and nonneuronal cells.
Where are the high affinity neurotrophin receptors found?
Only on Neurons
The high affinity receptor found on neurons is called
p140prototrk or simply trk ( produced by oncogenes)
Structure of trk
consists of:
- an extracellular domain with the neurotrophin-binding
site
- a short transmembrane segment,
- an intracellular domain encoding a tyrosine kinase
What are the 3 members of the trk family of proto-oncogenes?
1) Trk-A
2) Trk-B
3) Trk-C
Which neurotrophin is Trk- A a receptor for?
NGF
Which neurotrophin is Trk- B a receptor for?
BDNF and NT-4/5
Which neurotrophin is Trk- C a receptor for?
NT-3
What happens after binding of neurotrophin to its high affinity receptor?
1) an increase in tyrosine phosphorylation of the receptors themselves.
2) This activates three intracellular signaling pathways, phospholipase C, phosphatidylinositol-3-kinase, and the MAP kinase cascade.
How does low affinity receptor differ from High affinity receptor structurally?
lacks any intracellular domain
What is function of the low affinity receptor?
unknown
- may interact with the high affinity receptor during the binding of neurotrophins
- may trigger cell death, or provide a
mechanism for restricting diffusion and establishing high local concentrations
of neurotrophins, as during peripheral nerve regeneration.
Which areas of the CNS BDNF or NT-3 for survival?
Cells in the cortex and hippocampus
BNDF- retinal ganglion cell branching and remodeling,
dendritic growth of cortical neurons, and the formation of ocular dominance
columns in developing visual cortex
What is the hypothesis for apoptosis occurring during development?
Cells may be competing for vital substance released by the target
Polyneuronal innervation
During development muscle , which are singly innervated when mature , are innervated by multiple motoneurons until they are reduced by synapse elimination
Which cell mediates Reduction or elimination of polyneuronal innervation?
The muscle fiber
Other regions where Reduction of polyneuronal innervation occurs
Autonomic Nervous system and Cerebellum
Where do retinal ganglion cells grow towards
optic tectum
Ganglion cells from nasal retina innervate _________ tectum and cells from temporal retina innervate ________ tectum
posterior; anterior
What receptor is responsible for repulsive interaction of retinal ganglion cells?
Ephrin (Eph) receptor of tyrosine kinase receptors
What are the ligands expressed in tectum during formation of retinotectal connections?
Ephrin A-2 and Ephrin A-5
Concentration of Ephrin ligands is highest in _______ tectum and lowest in ________ tectum
posterior; anterior
__________ ganglion cells have highest ephrin receptors than __________ ganglion cells
Temporal ; Nasal
Matching of neurons to target is not rigid and can be changed by _________
experience after birth
Brodmann’s area for primary visual cortex
Area 17
visual input goes into which layer
Layer 4
What does a plastic occluder do ?
allows light but no form or contrast to go through
Stribismus
congenital squint
When muscles are denervated they get ______(more or less) sensitive to transmitter
More (supersensitive)
Why can’t CNS axons grow over long distances?
Partly due to proteins on surface of astrocytes and Oligodendrocytes that inhibit axon growth
Where is the primary and secondary effect of the drug thalidomide?
Primary- neurons
Secondary- bone growth=reduce appendages to flipper
What is the effect of albinism on neuronal development?
- alter axon growth and the formation of connections
- miswiring of retinogeniculate connections
What layer does notochord originate from?
mesoderm
What layer does neural plate, neural fold, neural tube and neural crest originate from?
ectoderm
Where would oldest neurons be found during development?
towards ventricular surface; young neurons pass by older ones
short range immobile factors promoting growth include
Laminin and NCAMs
Short range diffusible factors promoting growth include
Sonic hedgehog and netrin
Long range factors promoting growth include
NGF
immunosypathectomy caused by antibody to
NGF
What happens when one eye lid is closed immediately after birth?
shrinkage of columns supplied by that eye
failure of cortical cells to be driven by that eye
eventual blindness in that eye if lid not opened for more than 3 months
